Differences in visible light‐induced pigmentation according to wavelengths: a clinical and histological study in comparison with UVB exposure

The visible light spectrum is wide, and it can be hypothesized that all the wavelengths between 400–700 nm do not induce the same photobiological effects on pigmentation. We assessed the potential pro‐pigmenting effects of two single wavelengths located at both extremities of the visible spectrum: the blue/violet line (λ = 415 nm) and the red line (λ = 630 nm). We made colorimetric, clinical, and histological assessments with increasing doses of those lights on healthy volunteers. Then, we compared these irradiations to non‐exposed and UVB‐exposed skin. Colorimetric and clinical assessments showed a clear dose effect with the 415‐nm irradiation, in both skin type III and IV subjects, whereas the 630 nm did not induce hyperpigmentation. When compared to UVB irradiation, the blue–violet light induced a significantly more pronounced hyperpigmentation that lasted up to 3 months. Histological examination showed a significant increase of keratinocyte necrosis and p53 with UVB, as compared to 415‐ and 630‐nm exposures.     

Comparative study of human red blood cell analysis with three different field-flow fractionation systems

An extensive multi-laboratory study was conducted to compare three different field-flow fractionation (FFF) systems for use in the analysis of human erythrocytes. The object of this study was to determine the relationship between the FFF elution properties for each system and the traditional hematological blood cell parameters. One centrifugal system (Utah) and two gravitational systems (Paris and Abbott) were compared. In order to analyze erythrocyte populations with a broad range of hematological indices, blood samples were collected from individuals heterozygous for sickle cell anemia (A/S) and also from normal controls (A/A), and these were analyzed at each site. Identical samples were analyzed by the Abbott and Utah sites. With all three systems, blood samples from each category produced narrow, overlapping distributions of FFF retention ratios, with the Abbott and Utah systems showing slight elevations in the mean retention ratios for the sickle cell samples. Blood cell elution peak characteristics were compared with standard hematological parameters for each of the FFF systems, and negative correlations were consistently found between mean corpuscular volume (MCV) and retention ratios. Positive correlations were found between red cell distribution width (RDW) and retention ratios. Elevated FFF retention ratios were frequently found with blood samples having abnormal hematological profiles. These results demonstrate that the three differently configured systems all produce similar analysis profiles for erythrocytes from the classes studied here. The relationships between FFF parameters and hematological indices were consistent for all systems.     

C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity

The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer (NK) cells and granulocytes. The latter and most prevalent blood cell population contributes to phagocytosis, but is not effective in inducing ADCC. Here, we report that targeted delivery of the tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL. Upon CLL1-selective binding of this fusion protein, granulocytes acquire additional TRAIL-mediated cytotoxic activity that, importantly, potentiates antibody-mediated cytotoxicity of clinically used therapeutic antibodies (e.g., rituximab, cetuximab). Thus, CLL1:TRAIL could be used as an adjuvant to optimize the clinical potential of anticancer antibody therapy by augmenting tumoricidal activity of granulocytes.     

Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway

The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.     

Thermoregulatory control of feeding and sleep in premature infants

Objective: The aim of the present study was to test the thermoregulatory feeding control hypothesis in sleeping, premature infants. Research Methods and Procedures: In premature infants, the energy supply from food intake is crucial for (in order of importance): organ operation, body homeothermia, and optimal growth. The Himms‐Hagen model of thermoregulatory feeding control involving activation of heat production by brown adipose tissue (BAT) was formulated on the basis of work in (awake) rats. This hypothesis has also been put forward for the human neonate, which can also use BAT to produce metabolic heat. According to the model, feeding episodes occur during a transient increase in body temperature. Feeding is initiated by a dip in blood glucose concentration after sugar uptake by activated BAT. Results: In 14 neonates (bottle‐fed on demand), food intake always took place during an increase in skin temperature (+0.19 ± 0.21 °C). Awakening occurred 18 ± 17 minutes after the minimum skin temperature level had been reached. When feeding time was imposed, feeding was not necessarily situated during an increase in skin temperature, and the sleep duration after food intake increased significantly (+43%). This could be considered as an adaptive response to the short‐term sleep deprivation and/or stress elicited by an imposed feeding rhythm. Discussion: The validity of the model supports the use of on‐demand feeding in neonatal care units, in accordance with the infant's physiological body temperature oscillations.     

Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis

Introduction

Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination.

Methods

Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intraarticular glucocorticoid injection, and eight healthy volunteers. Synovial inflammation was assessed with double-blind semiquantitative analysis of lining thickness, cell infiltration, and vascularity by using a 4-point scale. Expression of citrullinated proteins (CPs) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically with double-blind semiquantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB), mononuclear cells (MCs), and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed with immunohistochemistry for expression of CP as well as PAD2 and PAD4 enzymes.

Results

The presence of synovial CP was almost exclusive in RA compared with healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination, as demonstrated by the decrease in the level of citrullination and PAD expression after incubation of SFMC and synovial explants with dexamethasone.

Conclusion

Synovial citrullination and PAD expression are dependent on local inflammation and targeted by glucocorticoids.     

A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis

Background  

The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway.     

Genome-assisted prediction of a quantitative trait measured in parents and progeny: application to food conversion rate in chickens

Accuracy of prediction of yet-to-be observed phenotypes for food conversion rate (FCR) in broilers was studied in a genome-assisted selection context. Data consisted of FCR measured on the progeny of 394 sires with SNP information. A Bayesian regression model (Bayes A) and a semi-parametric approach (Reproducing kernel Hilbert Spaces regression, RKHS) using all available SNPs (p = 3481) were compared with a standard linear model in which future performance was predicted using pedigree indexes in the absence of genomic data. The RKHS regression was also tested on several sets of pre-selected SNPs (p = 400) using alternative measures of the information gain provided by the SNPs. All analyses were performed using 333 genotyped sires as training set, and predictions were made on 61 birds as testing set, which were sons of sires in the training set. Accuracy of prediction was measured as the Spearman correlation (r¯S) between observed and predicted phenotype, with its confidence interval assessed through a bootstrap approach. A large improvement of genome-assisted prediction (up to an almost 4-fold increase in accuracy) was found relative to pedigree index. Bayes A and RKHS regression were equally accurate (r¯S = 0.27) when all 3481 SNPs were included in the model. However, RKHS with 400 pre-selected informative SNPs was more accurate than Bayes A with all SNPs.